Can Wellbutrin Cause Irritability?
Yes, Wellbutrin (bupropion) can cause irritability as a recognized adverse effect, documented in both FDA labeling and clinical studies.
Evidence from FDA Drug Labeling
The FDA label for bupropion explicitly lists irritability among the neuropsychiatric symptoms that have been reported in patients treated with antidepressants 1. Specifically, the following symptoms have been documented: anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania 1.
- Timing of onset: These symptoms can occur during the initial months of treatment or at times of dose changes 1
- Monitoring requirement: The FDA mandates that families and caregivers be alerted to monitor for the emergence of agitation, irritability, and unusual changes in behavior, with instructions to report such symptoms immediately to healthcare providers 1
- Clinical significance: While a causal link between irritability and worsening depression or suicidality has not been definitively established, there is concern that such symptoms may represent precursors to emerging suicidality 1
Clinical Trial Evidence
A retrospective study of 127 children and adolescents with depressive disorders found that irritability was the most common adverse event, occurring in 12 patients (9.4%) 2.
- In this pediatric population, irritability resolved spontaneously in eight subjects or required drug discontinuation in four subjects 2
- The mean bupropion dose was 180 mg/day (range 75-300 mg) 2
- Despite irritability being the most frequent side effect, the medication was generally well-tolerated overall 2
Mechanism and Context
Bupropion's mechanism involves inhibition of dopamine and norepinephrine reuptake 3. Common side effects include nervousness and insomnia, which may contribute to or overlap with irritability 3. The drug is generally considered safe and effective, with sexual dysfunction being less common than with SSRIs 3.
Clinical Management Considerations
When irritability emerges on bupropion:
- Assess severity and timing: Determine if symptoms are severe, abrupt in onset, or represent a change from baseline presentation 1
- Consider dose relationship: Irritability may be dose-dependent and could improve with dose reduction
- Evaluate for discontinuation: If irritability is severe or persistent, consider changing the therapeutic regimen, including possibly discontinuing the medication 1
- Monitor for escalation: Watch for progression to more serious neuropsychiatric symptoms such as hostility, aggressiveness, or suicidal ideation 1
Common pitfall: Delayed recognition of bupropion-related irritability, particularly when symptoms emerge after the initial weeks of treatment rather than immediately upon starting the medication 2.